Abstract 15637: Exposure to Traffic-Generated Air Pollutants Results in Disruption of the Blood Brain Barrier through Altered Expression of Tight Junction Proteins
In addition to its harmful effects in the pulmonary and cardiovascular systems, several recent studies have implicated environmental air pollution exposure in deleterious effects on the central nervous system (CNS), including neuroinflammation, stroke, and neurodegeneration. We have reported that vascular oxidative stress, oxidized LDL (oxLDL), and matrix metalloproteinase (MMP) levels are significantly elevated in the systemic vasculature of atherosclerotic apolipoprotein KO (ApoE-/-) mice exposed to vehicular emissions; however, the effects of exposure in the cerebral vasculature have not yet been examined. Numerous recent epidemiological and laboratory studies show a positive correlation between exposure to high levels of air pollution and increased hospital admissions/occurrence of cerebrovascular events (e.g. stroke, transient ischemic attack), with significant elevations in resulting morbidity and mortality. To determine whether traffic-generated air pollutants mediate disruption of the blood brain barrier (BBB) through altered expression of tight junction (TJ) protein expression, 10 wk old male ApoE-/- mice on a high fat diet were randomly assigned to an inhalation exposure of either filtered-air (FA: n=8 per time point) or an exposure of 250µg PM/m3 diesel exhaust + 50µg PM/m3 gasoline mixed engine exhaust (ME: n=8 per time point) for 6 hr/d for 7 or 30 d. Exposure to ME resulted in BBB integrity disruption as evidenced by increased FITC fluorescence in the brain, compared to FA controls, after systemic injection of FITC during exposures. Histological and molecular analysis showed a significant decrease in expression of BBB TJ proteins occuldin and claudin-5 in cerebral vessels with ME-exposure. Additionally, there was increased neurovascular MMP-2 and -9 activities shown by in situ zymography, and elevated cerebral iNOS expression, indicating neuroinflammation, in ME-exposed brains. Such findings indicate that inhalation exposure to traffic-generated air pollutants results in BBB disruption associated with increased MMP activity and decreased TJ protein expression.
- © 2012 by American Heart Association, Inc.